Anaplastic Lymphoma Kinase

Abstract

Anaplastic lymphoma kinase (ALK) is a transmembrane receptor tyrosine kinase, which is a member of the insulin receptor superfamily. Fusions in ALK result in constitutively activated signaling which is susceptible to inhibition by ALK tyrosine kinase inhibitors (TKIs). In this chapter we are describing management of patients with ALK-fused lung cancer. We will discuss molecular basis of ALK fusion including different fusion partners and variants, testing for ALK, targeting ALK with TKI, and managing resistance. Targeting ALK oncogenic driver has been an example of rapid drug development with the first ALK inhibitor approved in 2011 just 4 years after the first publication of ALK discovery by Soda et al. In the following years, we have discovered second- and third-generation ALK inhibitors which are able to circumvent ALK resistance and distinguished by better CNS penetration.